Dapirolizumab Pegol Shows Promise in Lupus During Phase 3 Trial, With Ed Vital, MD

At the ACR Convergence 2025, HCPLive spoke with Ed Vital, MD, a translational medicine expert at the University of Leeds, about the latest findings from the phase 3 PHOENYCS GO trial of dapirolizumab pegol (DZP) in systemic lupus erythematosus (SLE).1 DZP is a novel CD40 ligand inhibitor that modulates B cell activation and broader immune pathways, offering a distinct mechanism compared with existing therapies.2

“The is a new biologic for lupus that works in a different way from the drugs that we have already,” Vital told HCPLive. “It targets the interaction of a molecule called CD 40 and CD 40 ligand, and that's a target that's been of interest for a while, because we know it has a really important role in B cell activation, which is important in diseases like lupus, but we now recognize actually that CD 40 ligand interactions is involved in many different functions in the immune systems.”

These findings, presented at ACR 2025 in Chicago from October 24 – 29, 2025, suggest that DZP not only improves response rates but also supports sustained low disease activity and remission, underscoring its potential as a meaningful addition to the SLE treatment landscape.

PHOENYCS GO trial, a 48-week, randomized, double-blind, placebo-controlled study, evaluated DZP in patients aged ≥ 16 years with moderate-to-severe, active SLE despite stable standard-of-care therapy (antimalarials, glucocorticoids, and immunosuppressants).1 Patients were randomized 2:1 to receive DZP plus standard-of-care (SOC) or placebo plus SOC every 4 weeks. The primary endpoint, previously reported, showed a greater rate of BILAG-based Composite Lupus Assessment (BICLA) response with DZP versus placebo.

Vital highlighted that beyond overall response, the study assessed remission per the DORIS definition and low disease activity per the Lupus Low Disease Activity State (LLDAS). Results were encouraging: 40.9% of patients receiving DZP+SOC achieved LLDAS at week 48 versus 19.6% with placebo (P <.0001), and 23.6% of DZP-treated patients maintained LLDAS in at least half of their visits through week 48 versus 15.9% for placebo. The cumulative number of visits in LLDAS was also greater for DZP (2.9 vs 1.8; P =.0016). Achievement of DORIS was similarly improved, with 19.2% of DZP patients reaching remission at week 48 versus 8.4% with placebo (P =.0056); a greater proportion of patients on DZP vs placebo reached remission at weeks 20, 32, and 36 (P =.05).

Vital highlighted the difficulty of measuring flares in lupus, a disease marked by fluctuating activity. The trial used innovative flare definitions that tracked sequential disease activity over time rather than relying on isolated snapshots. This approach showed more flares in the placebo group and demonstrated that DZP stabilized disease activity, improving sustained low disease activity and remission rates. Vital explained that the analysis tested new ways to define moderate flares, allowing a more accurate understanding of DZP’s effects by capturing disease changes occurring at different times as part of a single flare event rather than single snapshots.

“What we said is, let's just look at flares that if they evolved over not 1 time point, but over 2,” Vital said. “When you do that, what happens is the number of flares you detect goes up. You find more, but you find a lot more on the placebo arm, and you don't see many more in the deeper realism map arm. In other words, the difference between the two treatments got greater and greater when we made this broader [flare] definition."

Vital has no relevant reported disclosures.

References

1. Morand E, Carter L, Dall'Era M, Petri M, Vital E, Jimenez T, Gaiha-Rohrbach J, Lauwerys B, Nelde A, Stach C, van Vollenhoven R. Achievement of Low Disease Activity and Remission in Patients with Systemic Lupus Erythematosus Treated with Dapirolizumab Pegol: 48-Week Results from a Phase 3 Trial [abstract]. Arthritis Rheumatol. 2025; 77 (suppl 9). https://acrabstracts.org/abstract/achievement-of-low-disease-activity-and-remission-in-patients-with-systemic-lupus-erythematosus-treated-with-dapirolizumab-pegol-48-week-results-from-a-phase-3-trial/. Accessed November 3, 2025.

2. Cutcutache I, Powlesland A, Skelton A, Sun Y, Page M, Stojan G, Lipsky P, Skowera A, Stach C. Dapirolizumab Pegol Impacts Important Immunologic Pathways in SLE: Pharmacodynamic Analysis of B Cell and Type I Interferon Pathways from a Phase 2b Trial [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/dapirolizumab-pegol-impacts-important-immunologic-pathways-in-sle-pharmacodynamic-analysis-of-b-cell-and-type-i-interferon-pathways-from-a-phase-2b-trial/. Accessed November 4, 2025.